biostudies-literatureKharrat ONational Centre for Scientific ResearchFrench Infrastructure for Integrated Structural Biology110587https://www.ebi.ac.uk/biostudies/studies/S-EPMC12455092biostudies-literatureUnknown301(9)The growing resistance to antifungal drugs and the limited number of antifungals currently available highlight the need for new antifungal strategies. In this context, there is significant potential for plant and insect antifungal defensins, which target fungal glucosylceramides (GlcCer), a growth and virulence determinant. The ETD151 peptide, optimized from the insect defensin Heliomicin, binds to fungal GlcCer as a crucial step in its activity. Nevertheless, further investigation is necessary to elucidate the mechanisms by which ETD151 targets fungal GlcCer at the molecular and atomic scales. The binding affinity was experimentally measured with isothermal titration calorimetry and microscale thermophoresis. The results collectively revealed affinity with a membrane-bound methylated GlcCThe Journal of biological chemistryMolecular recognition of fungal methylated glucosylceramides by ETD151 defensin.PMC12455092ANR-10-INBS-0005-02ANR-17-EURE-0003Paquet FMadinier JBAucagne VNehme RKharrat ONasreddine RBulet PLandon CWarschawski DfalseMolecular recognition of fungal methylated glucosylceramides by ETD151 defensin.The growing resistance to antifungal drugs and the limited number of antifungals currently available highlight the need for new antifungal strategies. In this context, there is significant potential for plant and insect antifungal defensins, which target fungal glucosylceramides (GlcCer), a growth and virulence determinant. The ETD151 peptide, optimized from the insect defensin Heliomicin, binds to fungal GlcCer as a crucial step in its activity. Nevertheless, further investigation is necessary to elucidate the mechanisms by which ETD151 targets fungal GlcCer at the molecular and atomic scales. The binding affinity was experimentally measured with isothermal titration calorimetry and microscale thermophoresis. The results collectively revealed affinity with a membrane-bound methylated GlcC2025-01-01T00:00:00Z2025 Aug2026-06-03T19:05:57.018Z2026-04-30T03:12:00.848ZS-EPMC124550924081242510.1016/j.jbc.2025.110587